Lymphotoxin-β receptor (LTβR), a non-death domain containing receptor of the tumor necrosis factor receptor (TNFR) family, is reported to play an important role in organogenesis of secondary lymphoid tissues. Two types of ligands for LTβR have been described. These have been identified as the heterotrimer LTα1β2 and the homotrimer LIGHT.
LTβR signaling is believed to be mediated by signaling molecules recruited to the intracellular domain of the receptor upon binding of a ligand. Like other members in the TNFR family, multiple signaling pathways are activated by the ligand-LTβR complex, including apoptosis, activation of NFκB and JNK pathway.
Apoptosis, or programmed cell death, is a normal cell suicide function. There are two major signaling pathways of apoptosis, the death receptor pathway and the mitochondrial pathway. Signals from both pathways lead to the activation of a common cascade of caspases, which subsequently cleave a large number of cellular proteins resulting in cell death. Most of the death domain-containing receptors induce apoptosis by recruitment of FADD and activation of caspase 8. In contrast, LTβR lacks a death domain sequence and thus does not interact with FADD. Moreover, the cell death induced by LTβR has a characteristic of a slow apoptosis process and is dependent on interferon γ. Therefore, LTβR-induced apoptosis is thought to be activated by mechanism that is distinct from a death domain-dependent mechanism.